Processes for making particle-based pharmaceutical formulations for oral administration

Abstract

A method is provided for making an oral dosage form of a pharmaceutical agent which includes the steps of (a) providing particles which include a pharmaceutical agent; (b) blending the particles with particles of a pre-processed excipient to form a primary blend, wherein the pre-processed excipient is prepared by (i) dissolving a bulking agent (e.g., a sugar) and at least one non-friable excipient (e.g., a waxy or liquid surfactant) in a solvent to form an excipient solution, and (ii) removing the solvent from the excipient solution to form the pre-processed excipient in dry powder form; (c) milling the primary blend to form a milled pharmaceutical formulation blend that includes microparticles or nanoparticles of the pharmaceutical agent; and (d) processing the milled pharmaceutical formulation blend into a solid oral dosage form or liquid suspension for oral administration. The process yields formulations having improved wettability or dispersibility.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims benefit of U.S. Provisional Application No. 60 / 750,750, filed Dec. 15, 2005. The application is incorporated herein by reference.BACKGROUND OF THE INVENTION [0002] This invention is generally in the field of pharmaceutical compositions comprising particles, such as microparticles, and more particularly to methods for making particulate blend formulations for oral administration. [0003] Microparticles comprising therapeutic and diagnostic agents are known to be useful for enhancing the controlled delivery of such agents to humans or animals. For these applications, microparticles having very specific sizes and size ranges are needed in order to effectively deliver these agents. Many drug formulations are produced in a dry powder form for use in one or more particular dosage forms. [0004] Oral dosage forms of therapeutic microparticles require that the microparticles disperse in vivo in the oral cavity (e.g., orall...

AI Technical Summary

Problems solved by technology

Microparticles, particularly those consisting of hydrophobic pharmaceutical agents, tend to be poorly dispersible in aqueous media.

This may undesirably alter the microparticle formulation's performance and / or reproducibility.

Combining these excipients with the microparticles can complicate production and scale-up; it is not a trivial matter to make such microparticle pharmaceutical formulations, particularly on a commercial scale.

Furthermore, certain desirable excipient materials are difficult to mill or blend with pharmaceutical agent microparticles.

For example, excipients characterized as liquid, waxy, non-crystalline, or non-friable are not readily blended uniformly with drug containing particles and / or are not readily processed through a mill.

Conventional dry blending of such materials may not yield the uniform, intimate mixtures of the components, which pharmaceutical formulations require.

Such consistency in a dry powder formulation may be difficult to achieve with an excipient that is not readily blended or milled.

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